The basis of antigenic specificity is stereochemical, as was first demonstrated by

Obermayer and Pick and confirmed by Landsteiner. Using haptens such as atoxyl coupled with protein, it was shown that antigenic specificity is determined

by single chemical groupings and even by a single acid radical. The importance of the position of the antigenic determinant group in the antigen molecule was evidenced by the differences in specificity in compounds with the group attached at the ortho, meta or para positions. The influence of spatial configuration of the determinant group was shown by differences in antigenic specificity of the dextro, levo and meso isomers of substances such as tartaric acid.

Antigenic specificity is not absolute. Cross-reactions can occur between antigens that bear stereochemical similarities. In some instances, apparent cross-reactions may actually be due to the sharing of identical antigenic determinants by different antigens.

The specificity of natural tissue antigens of animals may be considered under different categories as species, iso-, auto- and organ specificity.

1.Species specificity: Tissues of all individuals in a species contain species-specific antigens. There existssome degree of cross-reaction between antigens from related species. This immunological relationship parallels phylogenetic relationship. It has been used

in tracing evolutionary relationships between species. It also has forensic applications in the identification of the species of blood and of seminal stains. Phylogenetic relationships are reflected in the extent of cross reaction between antigens from different species that

cause hypersensitivity. An individual sensitised to horse serum will react with serum from other equines but may not do so with bovine serum,

2.Isospecificity: Antigen are antigens found in

some but not all members of a species. A species may be grouped depending on the presence of different isoantigens in its members. The best examples of isoantigens are the human erythrocyte antigens based

on which individuals can be classified into different blood groups. These are genetically determined. They are of clinical importance in blood transfusion and in isoimmunisation during pregnancy. They were help in determining disputed paternity cases, but have

been supplanted by the more discriminatory DNA fingerprinting tests. Blood groups find application in anthropology.

Histocompatibility antigens are those cellular

determinants specific to each individual of a species. They are recognised by genetically different individuals of the same species when attempts are made to transfer or transplant cellular material from one individual to

another.

3. Autospecificity: Autologous or self-antigens are ordinarily non antigenic but there are exceptions Sequestered antigens that are not normally found free in circulation or tissue fluid (such as eye lens protein normally confined within its capsule) are not recognised as self-antigens. Similarly, antigens that are absent during embryonic life and develop later (such as sperm) are also not recognised as self-antigens.

4. Organ specificity: Some organs, such as the brain, kidney and lens protein of different species, share the same antigen. Such antigens, characteristics of an organ or tissue and found in different species, are

called organ-specific antigens. The neuroparalytic complications following anti rabies vaccination using sheep brain vaccines are a consequence of brain-specific

antigens shared by sheep and human beings. The sheep brain antigens induce immunological response in the vaccinees, damaging their nervous tissue.

5.Heterogenetic (heterophile) specificity: The same or closely related antigens may sometimes occur in different biological species, classes and kingdoms. These are known as heterogenetic or heterophile

antigens, best exemplified by the Forssman antigen, which is a lipid carbohydrate complex widely distributed in many animals, birds, plants and bacteria. It is absent in rabbits, so anti-Forssman antibody can be prepared in these animals. Other heterophile antigens are responsible for some diagnostic serological

reactions in which antigens unrelated to etiological agents are employed (heterophile reaction). The Weil Felix reaction in typhus fever, the Paul Bunnell test in infectious mononucleosis and the cold agglutinin test

in primary atypical pneumonia are examples.